Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73631230" target="_blank" >RIV/61989592:15640/25:73631230 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/25:73631230

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0006349525003698?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0006349525003698?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpj.2025.06.009" target="_blank" >10.1016/j.bpj.2025.06.009</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system

Popis výsledku v původním jazyce

Tau aggregation into neurofibrillary tangles is a defining feature of Alzheimer&apos;s disease and other tauopathies. Although aggregation depends largely on specific amyloidogenic motifs (particularly VQIINK and VQIVYK) in repeated regions of tau microtubule-binding domains, how the primary sequence of adjacent repeats intrinsically influences aggregation and prion-like propagation remains unclear. This study systematically characterized three unmodified, physiologically relevant tau peptide constructs—R1R3, R2R3, and R3R4—to define their intrinsic aggregation kinetics, structural features, and prion-like seeding activity. Among these constructs, we found that R2R3 showed rapid aggregation, distinct β-sheet formation, and potent seeding capable of sustained secondary propagation in cellular biosensor assays. Whereas recent studies have highlighted chemically modified peptides (e.g., acetylated and phosphomimic peptides), our study emphasizes the importance of native, unmodified sequences as fundamental determinants in tau aggregation. Furthermore, these findings establish R2R3 as a robust minimal tau model, providing a valuable tool for mechanistic research and therapeutic screening in tau-related neurodegeneration.

Název v anglickém jazyce

Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system

Popis výsledku anglicky

Tau aggregation into neurofibrillary tangles is a defining feature of Alzheimer&apos;s disease and other tauopathies. Although aggregation depends largely on specific amyloidogenic motifs (particularly VQIINK and VQIVYK) in repeated regions of tau microtubule-binding domains, how the primary sequence of adjacent repeats intrinsically influences aggregation and prion-like propagation remains unclear. This study systematically characterized three unmodified, physiologically relevant tau peptide constructs—R1R3, R2R3, and R3R4—to define their intrinsic aggregation kinetics, structural features, and prion-like seeding activity. Among these constructs, we found that R2R3 showed rapid aggregation, distinct β-sheet formation, and potent seeding capable of sustained secondary propagation in cellular biosensor assays. Whereas recent studies have highlighted chemically modified peptides (e.g., acetylated and phosphomimic peptides), our study emphasizes the importance of native, unmodified sequences as fundamental determinants in tau aggregation. Furthermore, these findings establish R2R3 as a robust minimal tau model, providing a valuable tool for mechanistic research and therapeutic screening in tau-related neurodegeneration.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BIOPHYSICAL JOURNAL

ISSN

0006-3495

e-ISSN

1542-0086

Svazek periodika

124

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

2339-2346

Kód UT WoS článku

001539141500001

EID výsledku v databázi Scopus

2-s2.0-105008911384